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Computation predicts rapidly adapting mechanotransduction currents cannot account for tactile encoding in Merkel cell-neurite complexes
Distinct firing properties among touch receptors are influenced by multiple, interworking anatomical structures. Our understanding of the functions and crosstalk of Merkel cells and their associated neurites—the end organs of slowly adapting type I (SAI) afferents—remains incomplete. Piezo2 mechanically activated channels are required both in Merkel cells and in sensory neurons for canonical SAI responses in rodents; however, a central unanswered question is how rapidly inactivating currents give rise to sustained action potential volleys in SAI afferents. The computational model herein synthesizes mechanotransduction currents originating from Merkel cells and neurites, in context of skin mechanics and neural dynamics. Its goal is to mimic distinct spike firing patterns from wildtype animals, as well as Atoh1 knockout animals that completely lack Merkel cells. The developed generator function includes a Merkel cell mechanism that represents its mechanotransduction currents and downstream voltage-activated conductances (slower decay of current) and a neurite mechanism that represents its mechanotransduction currents (faster decay of current). To mimic sustained firing in wildtype animals, a longer time constant was needed than the 200 ms observed for mechanically activated membrane depolarizations in rodent Merkel cells. One mechanism that suffices is to introduce an ultra-slowly inactivating current, with a time constant on the order of 1.7 s. This mechanism may drive the slow adaptation of the sustained response, for which the skin’s viscoelastic relaxation cannot account. Positioned within the sensory neuron, this source of current reconciles the physiology and anatomical characteristics of Atoh1 knockout animals
Recommended from our members
Computation predicts rapidly adapting mechanotransduction currents cannot account for tactile encoding in Merkel cell-neurite complexes
Distinct firing properties among touch receptors are influenced by multiple, interworking anatomical structures. Our understanding of the functions and crosstalk of Merkel cells and their associated neurites—the end organs of slowly adapting type I (SAI) afferents—remains incomplete. Piezo2 mechanically activated channels are required both in Merkel cells and in sensory neurons for canonical SAI responses in rodents; however, a central unanswered question is how rapidly inactivating currents give rise to sustained action potential volleys in SAI afferents. The computational model herein synthesizes mechanotransduction currents originating from Merkel cells and neurites, in context of skin mechanics and neural dynamics. Its goal is to mimic distinct spike firing patterns from wildtype animals, as well as Atoh1 knockout animals that completely lack Merkel cells. The developed generator function includes a Merkel cell mechanism that represents its mechanotransduction currents and downstream voltage-activated conductances (slower decay of current) and a neurite mechanism that represents its mechanotransduction currents (faster decay of current). To mimic sustained firing in wildtype animals, a longer time constant was needed than the 200 ms observed for mechanically activated membrane depolarizations in rodent Merkel cells. One mechanism that suffices is to introduce an ultra-slowly inactivating current, with a time constant on the order of 1.7 s. This mechanism may drive the slow adaptation of the sustained response, for which the skin’s viscoelastic relaxation cannot account. Positioned within the sensory neuron, this source of current reconciles the physiology and anatomical characteristics of Atoh1 knockout animals
Percutaneous closure of atrial septal defects leads to normalisation of atrial and ventricular volumes
Background: Percutaneous closure of atrial septal defects (ASDs) should potentially reduce right heart volumes by removing left-to-right shunting. Due to ventricular interdependence, this may be associated with impaired left ventricular filling and potentially function. Furthermore, atrial changes post-ASD closure have been poorly understood and may be important for understanding risk of atrial arrhythmia post-ASD closure. Cardiovascular magnetic resonance (CMR) is an accurate and reproducible imaging modality for the assessment of cardiac function and volumes. We assessed cardiac volumes pre- and post-percutaneous ASD closure using CMR. Methods: Consecutive patients (n = 23) underwent CMR pre- and 6 months post-ASD closure. Steady state free precession cine CMR was performed using contiguous slices in both short and long axis views through the ASD. Data was collected for assessment of left and right atrial, ventricular end diastolic volumes (EDV) and end systolic volumes (ESV). Data is presented as mean ± SD, volumes as mL, and paired t-testing performed between groups. Statistical significance was taken as p < 0.05. Results: There was a significant reduction in right ventricular volumes at 6 months post-ASD closure (RVEDV: 208.7 ± 76.7 vs. 140.6 ± 60.4 mL, p < 0.0001) and RVEF was significantly increased (RVEF 35.5 ± 15.5 vs. 42.0 ± 15.2%, p = 0.025). There was a significant increase in the left ventricular volumes (LVEDV 84.8 ± 32.3 vs. 106.3 ± 38.1 mL, p = 0.003 and LVESV 37.4 ± 20.9 vs. 46.8 ± 18.5 mL, p = 0.016). However, there was no significant difference in LVEF and LV mass post-ASD closure. There was a significant reduction in right atrial volumes at 6 months post-ASD closure (pre-closure 110.5 ± 55.7 vs. post-closure 90.7 ± 69.3 mL, p = 0.019). Although there was a trend to a decrease in left atrial volumes post-ASD closure, this was not statistically significant (84.5 ± 34.8 mL to 81.8 ± 44.2 mL, p = NS). Conclusion: ASD closure leads to normalisation of ventricular volumes and also a reduction in right atrial volume. Further follow-up is required to assess how this predicts outcomes such as risk of atrial arrhythmias after such procedures.Karen SL Teo, Benjamin K Dundon, Payman Molaee, Kerry F Williams, Angelo Carbone, Michael A Brown, Matthew I Worthley, Patrick J Disney, Prashanthan Sanders and Stephen G Worthle
Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
We report a quasi-differential upper limit on the extremely-high-energy (EHE)
neutrino flux above GeV based on an analysis of nine years of
IceCube data. The astrophysical neutrino flux measured by IceCube extends to
PeV energies, and it is a background flux when searching for an independent
signal flux at higher energies, such as the cosmogenic neutrino signal. We have
developed a new method to place robust limits on the EHE neutrino flux in the
presence of an astrophysical background, whose spectrum has yet to be
understood with high precision at PeV energies. A distinct event with a
deposited energy above GeV was found in the new two-year sample, in
addition to the one event previously found in the seven-year EHE neutrino
search. These two events represent a neutrino flux that is incompatible with
predictions for a cosmogenic neutrino flux and are considered to be an
astrophysical background in the current study. The obtained limit is the most
stringent to date in the energy range between and GeV. This result constrains neutrino models predicting a three-flavor
neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\
{\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}10^9\ {\rm GeV}$. A significant part
of the parameter-space for EHE neutrino production scenarios assuming a
proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review
Measurement of Rapidity Distribution for High Mass Drell-Yan ee Pairs at CDF
We report on the first measurement of the rapidity distribution dsigma/dy
over nearly the entire kinematic region of rapidity for e^+e^- pairs in the
Z-boson region of 66116 GeV/c^2.
The data sample consists of 108 pb^{-1} of ppbar collisions at \sqrt{s}=1.8 TeV
taken by the Collider Detector at Fermilab during 1992--1995. The total cross
section in the -boson region is measured to be 252 +- 11 pb. The measured
total cross section and d\sigma/dy are compared with quantum chromodynamics
calculations in leading and higher orders.Comment: 7 pages, 3 figures. Submitted to Physical Review Letter
Search for New Particles Decaying to Dijets at CDF
We have used 106 pb^-1 of data collected with the Collider Detector at
Fermilab to search for new particles decaying to dijets. We exclude at the 95%
confidence level models containing the following new particles: axigluons and
flavor universal colorons with mass between 200 and 980 GeV/c, excited quarks
with mass between 80 and 570 GeV/c^2 and between 580 and 760 GeV/c^2, color
octet technirhos with mass between 260 and 480 GeV/c^2, W' bosons with mass
between 300 and 420 GeV/c^2, and E_6 diquarks with mass between 290 and 420
GeV/c^2.Comment: 18 pages, 4 figures, 1 table. Submitted to Physical Review D Rapid
Communications. Postscript file of paper is also available at
http://www-cdf.fnal.gov/physics/pub97/cdf3276_dijet_search_prd_rc.p
Measurement of the lepton charge asymmetry in W-boson decays produced in p-pbar collisions
We describe a measurement of the charge asymmetry of leptons from W boson
decays in the rapidity range 0 enu, munu events from
110+/-7 pb^{-1}of data collected by the CDF detector during 1992-95. The
asymmetry data constrain the ratio of d and u quark momentum distributions in
the proton over the x range of 0.006 to 0.34 at Q2 \approx M_W^2. The asymmetry
predictions that use parton distribution functions obtained from previously
published CDF data in the central rapidity region (0.0<|y_l|<1.1) do not agree
with the new data in the large rapidity region (|y_l|>1.1).Comment: 13 pages, 3 tables, 1 figur
Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF
If the Technicolor omega_T particle exists, a likely decay mode is omega_T ->
gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We
have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab
Tevatron for events with a photon and two jets, where one of the jets must
contain a secondary vertex implying the presence of a b quark. We find no
excess of events above standard model expectations. We express the result of an
exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs):
http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps
FERMILAB-PUB-98/321-
Measurement of the Lifetime Difference Between B_s Mass Eigenstates
We present measurements of the lifetimes and polarization amplitudes for B_s
--> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and
light (L) mass eigenstates in the B_s system are separately measured for the
first time by determining the relative contributions of amplitudes with
definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we
obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07
+{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s
and average Gamma_s, of the decay rates of the two eigenstates, the results are
DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47
+{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters
on 16 March 2005; revisions are for length and typesetting only, no changes
in results or conclusion
Measurement of and Production in Collisions at = 1.96 TeV
The Standard Model predictions for and production are
tested using an integrated luminosity of 200 pb of \ppbar collision data
collected at the Collider Detector at Fermilab. The cross sections are measured
selecting leptonic decays of the and bosons, and photons with
transverse energy GeV that are well separated from leptons. The
production cross sections and kinematic distributions for the and
are compared to SM predictions.Comment: 7 pages, 4 figures, submitted to PR
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